Lower metachronous gastric cancer risk after H. pylori treatment
A South Korean study has shown that patients with early gastric cancer who received Helicobacter pylori (H. pylori) eradication therapy were less likely to develop metachronous gastric cancer.
“[T]he incidence of metachronous gastric cancer was approximately 50 percent lower among patients who had received treatment for H. pylori infection than among those who had received placebo,” said the authors led by Dr Il Ju Choi from the National Cancer Center in Goyang, South Korea.
Researchers of this single-centre, prospective, double-blind trial randomized 470 patients aged 18–75 years to receive either H. pylori eradication therapy (amoxicillin 1,000 mg, clarithromycin 500 mg, and rabeprazole 10 mg BID for 7 days) or placebo (rabeprazole 10 mg plus placebo pills) within 1 week of undergoing endoscopic resection of early gastric cancer or high-grade adenoma. Patients in both groups continued rabeprazole for an additional 4 weeks after the treatment period.
Of these, 396 patients were included in the intention-to-treat population (n=194 and 202 on eradication therapy and placebo, respectively) and were followed up over a median 5.9 years, during which there were 41 cases of metachronous gastric cancer. Endoscopy was conducted at 3 months, 6 months, and 1 year followed by every 6 months or 12 months.
Patients who had previously received H. pylori treatment, those with recurrent gastric cancer, and those with cancer of another organ in the last 5 years were among those excluded.
Significant risk reduction after H. pylori treatment
The incidence of metachronous gastric cancer was lower among patients who received H. pylori treatment compared with those who received placebo (7.2 percent vs 13.4 percent; p=0.03, hazard ratio [HR], 0.50, 95 percent confidence interval [CI], 0.26–0.94). [N Engl J Med 2018;378:1085-1095]
Metachronous gastric cancer was less likely to occur in patients whose H. pylori infection was eradicated compared with those with persistent infection (9.1 vs 27.9 cases per 1,000 person-years; p=0.003).
Of the 327 patients who underwent endoscopic biopsy at 3-year follow up, compared with patients who received placebo, more patients who received H. pylori treatment experienced improvement from baseline in glandular atrophy grade at the gastric corpus lesser curvature (48.4 percent vs 15.0 percent, odds ratio [OR], 5.30, 95 percent CI, 3.08–9.13; p<0.001). Improvement in intestinal metaplasia at the corpus lesser curvature was also more common among patients who received H. pylori treatment compared with those who received placebo (36.6 percent vs 18.3 percent, OR, 2.58; p<0.001).
Metachronous gastric adenoma incidence was similar between patients who received H. pylori treatment and placebo (n=16 and 17, respectively), as was all-cause mortality (n=11 vs 6, HR, 1.95; p=0.19).
No serious adverse events (AEs) occurred over the trial period. Mild treatment-related AEs occurred more frequently in patients who received H. pylori treatment than placebo (42.0 percent vs 10.2 percent; p<0.001).
According to the authors, “persistent inflammation of gastric mucosa with H. pylori infection promotes carcinogenesis” and may also have a role to play in increasing tumour growth or invasiveness.
“The beneficial effect may also be mediated by an alteration in the composition of the gastric microbiota because of improvement in the grade of gastric atrophy and a return toward normal gastric acid production,” added Professor Peter Malfertheiner from the Otto von Guericke University Magdeburg, Germany, in an editorial. [N Engl J Med 2018;378:1154-1156]
The authors cautioned that as H. pylori eradication does not completely eliminate metachronous gastric cancer risk, the use of molecular markers “might help to identify high-risk patients even after successful eradication”.
Malfertheiner also highlighted the importance of endoscopic or histologic surveillance as the reduced risk may only affect a subgroup of patients and advocated for bismuth-based therapies to reduce the risk of antimicrobial resistance.
Potential benefit in East Asia
While the single-centre design may pose a limitation, the findings could still be applicable to countries with a high incidence of gastric cancer, said the authors.
“The most relevant new target in gastric cancer prevention is H. pylori infection,” said Malfertheiner. Based on previous research that has demonstrated a reduced mortality rate following screening to detect gastric cancer at an earlier and more curable stage, [Gastroenterology 2017;152:1319-1328] the findings could have a significant impact in East Asia which shoulders two-thirds of the global burden of gastric cancer, he said.
“This study now proves that by eradicating H. pylori in the remnant gastric mucosa, risk of metachronous cancer can be reduced. This is good news for patients with early gastric cancer,” said gastroenterologist Dr Desmond Wai from Mount Elizabeth Novena Specialist Centre, Singapore.
“[However] we ought to be aware that early gastric cancer, though common in Japan and Korea, is relatively rare in the rest of the world. Most early gastric cancer cases are diagnosed on gastric cancer screening through routine endoscopies, which is not a common practice outside Japan,” said Wai, who was not affiliated with the study.
According to Wai, patients with treated early gastric cancer would be surveyed very regularly and as such, eradication of H. pylori will not change post-resection screening practices. Furthermore, most family physicians and gastroenterologists would eradicate H. pylori infection once it is diagnosed even in patients without gastric cancer, he said.